The blood flow in the optic nerve head is normally autoregulated, little affected by the level of intraocular pressure (IOP). Such regulation may be achieved through response to tissue levels of oxygen and carbon dioxide, which reflect the balance between local tissue metabolism and the volume of local blood flow. Hypothetically in glaucoma this regulation is faulty in the optic nerve head, permitting ischemic damage when the circulation is challenged by elevation of IOP. Only a little is known of the local physiologic events by which autoregulation is achieved, but nothing about how it may become faulty, or how faulty autoregulation might be corrected. Vascular smooth muscle of arteries and arterioles and precapillary sphincters have considerable influence on distribution of blood flow to various tissue regions. We hypothesize that capillaries may provide local fine tuning of blood flow, at least in some tissues. If capillaries participate in local control of blood flow, it may be achieved through pericytes, contractile cells whose function is not known, found in the walls of capillaries, especially in the central nervous system, including retina and optic nerve. In this project we plan to study the contractile response of pericytes grown in cell culture to metabolic signals that may permit them to participate in local control of the blood flow. The signals to be studied first are changes in carbon dioxide levels and the change in pH that accompanies changes in carbon dioxide levels. Responses to be observed are cell contraction, changes in intracellular pH, and changes in intracellular free calcium concentration.